Q08351 · TPOR_MOUSE
- ProteinThrombopoietin receptor
- GeneMpl
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids625 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Receptor for thrombopoietin that regulates hematopoietic stem cell renewal, megakaryocyte differentiation, and platelet formation (PubMed:8630375, PubMed:9122198, PubMed:9639492).
Upon activation by THPO, induces rapid tyrosine phosphorylation and activation of JAK2, providing docking sites for many signaling proteins such as STAT5, SHIP/INPP5D, GRB2, SOS1 and PI3K. In turn, These signaling cascades lead to the proliferation, survival, and differentiation of megakaryocytes, ultimately leading to increased platelet production
Upon activation by THPO, induces rapid tyrosine phosphorylation and activation of JAK2, providing docking sites for many signaling proteins such as STAT5, SHIP/INPP5D, GRB2, SOS1 and PI3K. In turn, These signaling cascades lead to the proliferation, survival, and differentiation of megakaryocytes, ultimately leading to increased platelet production
Isoform Mpl-tr
Acts as an inhibitor of thrombopoietin signaling by promoting protein down-regulation of full-length isoform Mpl-fl.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cell surface | |
Cellular Component | Golgi apparatus | |
Cellular Component | plasma membrane | |
Molecular Function | thrombopoietin receptor activity | |
Biological Process | definitive hemopoiesis | |
Biological Process | homeostasis of number of cells | |
Biological Process | negative regulation of apoptotic process | |
Biological Process | platelet formation | |
Biological Process | positive regulation of gene expression | |
Biological Process | regulation of chemokine production | |
Biological Process | regulation of stem cell division | |
Biological Process | regulation of stem cell proliferation | |
Biological Process | thrombopoietin-mediated signaling pathway |
Keywords
- Molecular function
Names & Taxonomy
Protein names
- Recommended nameThrombopoietin receptor
- Short namesTPO-R
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ08351
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type I membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Topological domain | 26-482 | Extracellular | |||
Transmembrane | 483-504 | Helical | |||
Topological domain | 505-625 | Cytoplasmic | |||
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mpl-deletion mice produce residual numbers of platelets that are sufficient to prevent bleeding and allow normal survival.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Mutagenesis | 104 | Completely abrogated binding to THPO. | |||
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 46 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for signal, chain, glycosylation, cross-link, modified residue.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Signal | 1-25 | ||||
Chain | PRO_0000010988 | 26-625 | Thrombopoietin receptor | ||
Glycosylation | 117 | N-linked (GlcNAc...) asparagine | |||
Cross-link | 544 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
Cross-link | 564 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) | |||
Modified residue | 616 | Phosphotyrosine | |||
Modified residue | 621 | Phosphotyrosine | |||
Post-translational modification
Ubiquitination at Lys-544 and Lys-564 targets MPL for degradation by both the lysosomal and proteasomal pathways. The E3 ubiquitin-protein ligase CBL significantly contributes to this ubiquitination.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Induction
Expression in the bone marrow displays diurnal rhythmicity (a circadian rhythm that is synchronized with the day/night cycle).
Gene expression databases
Interaction
Subunit
Homodimer (PubMed:38326297).
Interacts with ATXN2L. Interacts with JAK2 and TYK2; these interactions increase MPL localization to the cell membrane. Interacts with THPO (PubMed:38326297).
Interacts with SHIP/INPP5D. Interacts with kinases BTK and SYK (By similarity).
Interacts with ATXN2L. Interacts with JAK2 and TYK2; these interactions increase MPL localization to the cell membrane. Interacts with THPO (PubMed:38326297).
Interacts with SHIP/INPP5D. Interacts with kinases BTK and SYK (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, motif.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Domain | 178-270 | Fibronectin type-III 1 | |||
Domain | 383-479 | Fibronectin type-III 2 | |||
Motif | 465-469 | WSXWS motif | |||
Motif | 519-527 | Box 1 motif | |||
Domain
The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
The box 1 motif is required for JAK interaction and/or activation.
Sequence similarities
Belongs to the type I cytokine receptor family. Type 1 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
Q08351-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameMpl-fl
- SynonymsMpl-full-length
- Length625
- Mass (Da)69,788
- Last updated2011-07-27 v2
- MD5 ChecksumE6F0F2183BE99FA18589D041DD674FDF
Q08351-2
- NameMpl-tr
- SynonymsMpl-truncated
- NoteRbm15 regulates the production of isoform Mpl-tr.
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, alternative sequence.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Sequence conflict | 1-7 | in Ref. 2; CAA52031 | |||
Sequence conflict | 99 | in Ref. 2; CAA52031 | |||
Sequence conflict | 222 | in Ref. 2; CAA52031 | |||
Sequence conflict | 241 | in Ref. 1; CAA80365, 2; CAA52031 and 5; AAI46614 | |||
Alternative sequence | VSP_059621 | 428-457 | in isoform Mpl-tr | ||
Alternative sequence | VSP_059622 | 458-625 | in isoform Mpl-tr | ||
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Z22649 EMBL· GenBank· DDBJ | CAA80365.1 EMBL· GenBank· DDBJ | mRNA | ||
Z22657 EMBL· GenBank· DDBJ | CAA80372.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X73677 EMBL· GenBank· DDBJ | CAA52031.1 EMBL· GenBank· DDBJ | mRNA | ||
AK041166 EMBL· GenBank· DDBJ | BAC30846.1 EMBL· GenBank· DDBJ | mRNA | ||
AL627212 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC146613 EMBL· GenBank· DDBJ | AAI46614.1 EMBL· GenBank· DDBJ | mRNA |